肺腺癌组织RUNX3基因甲基化和蛋白表达与新辅助化疗敏感性的临床观察  

Clinical observation of RUNX3 gene methylation and protein expression and sensitivity to neoadjuvant chemotherapy in lung adenocarcinoma tissue

作　　者：金辉[1] 耿楠[2] 于凡[3] JIN Hui;GENG Nan;YU Fan(Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050012,China)

机构地区：[1]河北医科大学第四医院肿瘤内科,石家庄050012 [2]河北医科大学第四医院呼吸内科,050012 [3]河北医科大学第四医院胸外科,050012

出　　处：《临床肿瘤学杂志》2021年第2期128-133,共6页Chinese Clinical Oncology

基　　金：河北省医学科学研究重点课题资助项目(20160164)。

摘　　要：目的探讨肺腺癌组织runt结构域相关基因亚型3(RUNX3)甲基化状态和蛋白表达与新辅助化疗敏感性的关系。方法收集我院2018年9月至2019年9月就诊的116例ⅢA/ⅢB期肺腺癌患者的纤维支气管镜检组织标本,另收集30例肺鳞癌组织和30例肺部良性病变组织标本。采用免疫组化染色法和甲基化特异性PCR(MSP)检测组织中RUNX3蛋白表达和RUNX3甲基化状态。所有患者均完成2个周期新辅助化疗,采用RECIST 1.1版标准评价疗效。分析RUNX3蛋白表达和RUNX3甲基化状态与肺腺癌临床病理特征的关系。结果 TCGA数据库分析结果显示,RUNX3 mRNA在肺腺癌组织中表达显著下调(P<0.001)。RUNX3高表达组患者总生存率和无进展生存率优于RUNX3低表达组,差异有统计学意义(P<0.05)。良性对照组、肺鳞癌组、肺腺癌组组织RUNX3蛋白阴性表达率分别为3.33%(1/30)、23.33%(7/30)和55.17%(64/116),差异有统计学意义(P<0.001)。良性对照组、肺鳞癌组、肺腺癌组RUNX3基因甲基化率分别为10.0%(3/30)、16.67%(5/30)和31.90%(37/116),差异有统计学意义(P<0.05)。经Kappa一致性分析,肺腺癌组织RUNX3基因甲基化与RUNX3蛋白低表达结果一致性一般(Kappa=0.551,P<0.001)。肺腺癌组织RUNX3 mRNA甲基化和蛋白表达与吸烟史、新辅助化疗疗效有关(P<0.05)。结论 RUNX3基因在肺腺癌中呈高甲基化状态,是导致RUNX3蛋白表达下降的原因之一;RUNX3基因甲基化状态、RUNX3蛋白表达可以预测新辅助化疗疗效。Objective To investigate the gene methylation and protein expression of runx-domain-related subunit 3(RUNX3) in lung adenocarcinoma and its relation with the sensitivity to neoadjuvant chemotherapy. Methods A total of 116 patients with stage ⅢA/ⅢB lung adenocarcinoma admitted to our hospital from September 2018 to September 2019 were collected for fiberoptic bronchoscopy tissue specimens. In addition,30 lung squamous cell carcinoma tissue specimens and 30 benign lung lesions tissue specimens were collected. Immunohistochemical staining and methylation-specific PCR(MSP) were used to detect the expression of RUNX3 protein and the methylation status of RUNX3 in tissues. All patients completed 2 cycles of neoadjuvant chemotherapy,and the efficacy was evaluated by RECIST 1. 1 standard. To analyze the relationship between RUNX3 protein expression and RUNX3 methylation status and clinicopathological features of lung adenocarcinoma. Results TCGA database analysis showed that RUNX3 mRNA expression was significantly down-regulated in lung adenocarcinoma tissues(P< 0. 001). The overall survival rate and progression-free survival rate in the group with high expression of RUNX3 were better than those in the group with low expression of RUNX3,with statistical significance(P< 0. 05). The negative expression rates of RUNX3 protein in benign control group,lung squamous cell carcinoma group and lung adenocarcinoma group were 3. 33%(1/30),23. 33%(7/30) and 55. 17%(64/116),respectively,and the difference was statistically significant(P<0. 001). The methylation rates of RUNX3 gene in benign control group,lung squamous cell carcinoma group and lung adenocarcinoma group were 10. 0%(3/30),16. 67%(5/30) and 31. 90%(37/116),respectively,and the difference was statistically significant(P<0. 05). Kappa consistency analysis showed that the results of RUNX3 methylation and RUNX3 protein low expression in lung adenocarcinoma tissues were generally consistent(Kappa = 0. 551,P<0. 001).Runx3 mRNAmethylation and protein expression in lung aden

关 键 词：肺腺癌 RUNX3 甲基化 蛋白表达 新辅助化疗疗效 

分 类 号：R734.2[医药卫生—肿瘤]